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Menopausal Status Dependence of Early Mortality Reduction Due to Diagnosis of Smaller Breast Cancers (T1 v T2-T3): Relevance to Screening

From the Istituto Nazionale Tumori, Milano, Italy; Department of Surgery, Children's Hospital and Harvard Medical School, Boston, MA; and Dorn VA Medical Center, Columbia, SC.

Address reprint requests to Romano Demicheli MD, PhD, Istituto Nazionale Tumori, Department of Medical Oncology, Via Venezian 1, 20137 Milano, Italy; e-mail: demicheli{at}istitutotumori.mi.it

PURPOSE: To provide data relevant to the paradoxical mortality excess for women age 40 to 49 years observed during the first 6 to 8 years in the invited group in all mammography screening studies.

PATIENTS AND METHODS: In 1,173 patients undergoing mastectomy alone as primary treatment, allocated to subsets according to menopausal status and tumor size, hazard rates for death were calculated. The ratios between the hazard rate for T2-T3 patients and the corresponding value for T1 patients were assessed over time.

RESULTS: For postmenopausal patients, the ratio appeared to be time-dependent, dropping from the maximum value of approximately 5 at the first year after surgery to a near constant value of approximately 2 after 5 to 6 years. Premenopausal patients, on the contrary, showed a nearly constant ratio of approximately 3. Therefore, although in each T-category the 10-year survival of premenopausal and postmenopausal patients was similar, its time distribution was menopause-dependent. In particular, the difference between cumulative survival of premenopausal and postmenopausal T2-T3 patients attained statistical significance after 3 years.

CONCLUSION: The mortality reduction due to the diagnosis of smaller tumors is significantly higher for postmenopausal women than for premenopausal women during early postsurgery time. According to the hypothesis that primary tumor surgical removal, occurring sooner in the invited group than in the control arm of screening trials, results in some acceleration of metastasis development, a greater number of unfavorable events (recurrence and death) should occur in the invited group. We suggest that for younger women, the early balance between benefit from tumor downsizing and harm from surgery-induced metastasis acceleration results in harm. This disadvantage does not occur in postmenopausal women.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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